Localized Changes in LHRH mRNA Levels as Cellular Correlates of the Positive Feedback Effects of Estrogen on LHRH Neurons

Abstract

SYNOPSIS. The luteinizing hormone-releasing hormone (LHRH) system appears to be the final common pathway for integrating multiple estrogeninduced signals into a trigger for the preovulatory LH surge. Because LHRH neurons do not contain estrogen receptors, we have had no cellular marker to identify LHRH neurons involved in triggering the LH surge. Using an estrogenized ovariectomized rat model, we selectively deprived brain regions of estrogen action with microimplants of antiestrogen. We showed that the rostral medial preoptic area (MPOA) is required for estrogen-dependent LH surges and that LHRH neurons in this region are involved in the surge. Using in situ hybridization histochemistry, we compared temporal changes in LHRH mRNA levels in MPOA neurons in animals exhibiting LH surges with those in which LH surges were absent. We defined a characteristic pattern of changes in LHRH mRNA seen only in animals exhibiting the surge and, therefore, believe that these changes in LHRH mRNA levels are cellular correlates of the positive feedback effects of estrogen on LHRH neurons. These findings are exciting because we now have a cellular marker for detecting changes in the neuronal activity of subpopulations of the anatomically and functionally diverse LHRH system. We can use this marker in future studies to definethe complex neurocircuitry which mediates the effects of estrogen on LHRH neurons. In addition, we are currently examining temporal changes in LHRH transcription rate, LHRH mRNA stability and LHRH translation to determine the significance of changes in LHRH mRNA levels in terms of biosynthesis